Physical Electronics

Contains reports on three research projects

Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses and Cell-Penetrating Studies

A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme

Transient Ru-Methyl Formate Intermediates Generated with Bifunctional Transfer Hydrogenation Catalysts

Desorption electrospray ionization (DESI) coupled to high-resolution Orbitrap mass spectrometry (MS) was used to study the reactivity of a (β-amino alcohol)(arene)RuCl transfer hydrogenation catalytic precursor in methanol (CH3OH). By placing [(p-cymene)RuCl2]2 on a surface and spraying a solution of β-amino alcohol in methanol, two unique transient intermediates having lifetimes in the submillisecond to millisecond range were detected. These intermediates were identified as Ru (II) and Ru (IV) complexes incorporating methyl formate (HCOOCH3). The Ru (IV) intermediate is not observed when the DESI spray solution is sparged with Ar gas, indicating that O2 dissolved in the solvent is necessary for oxidizing Ru (II) to Ru (IV). These proposed intermediates are supported by high-resolution and high mass accuracy measurements and by comparing experimental to calculated isotope profiles. Additionally, analyzing the bulk reaction mixture using gas chromatography-MS and nuclear magnetic resonance spectroscopy confirms the formation of HCOOCH3. These results represent an example that species generated from the (β-amino alcohol)(arene)RuCl (II) catalytic precursor can selectively oxidize CH3OH to HCOOCH3. This observation leads us to propose a pathway that can compete with the hydrogen transfer catalytic cycle. Although bifunctional hydrogen transfer with Ru catalysts has been well-studied, the ability of DESI to intercept intermediates formed in the first few milliseconds of a chemical reaction allowed identification of previously unrecognized intermediates and reaction pathways in this catalytic system

Designed Guanidinium-Rich Amphipathic Oligocarbonate Molecular Transporters Complex, Deliver and Release siRNA in Cells

The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications

Physical Electronics

Contains reports on three research projects

Physical Electronics

Contains reports on three research projects

Physical Electronics

Contains reports on three research projects

Physical Electronics

Contains reports on three research projects

Chemical conversions in supercritical media: Environmentally sound approaches to processes and materials

This is the final report of a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The aim of this effort was to evaluate the potential of supercritical fluids (SCF) as reaction media in an effort to develop new, environmentally-friendly methods for chemical synthesis or processing. The use of novel media creates the possibility of opening up substantially different chemical pathways, increasing selectivity (eliminating waste by-products), and enhancing reaction rates (decreasing hold-up times and saving energy). In addition, the use of SCF as reaction media facilitates downstream separations and mitigate or eliminate the need for hazardous solvents on scales from bench top to production. This project employed a highly interdisciplinary approach to investigate the utility of SCFs as reaction media for polymer synthesis and synthetic organic chemistry